Micro pumps have been proposed for delivering medication particularly in applications where the dosing accuracy is very high and there is a requirement for portability of the medication system. While a number of micro pump designs have been described, pulsatile micro pumps have found applications in medication delivery.
A micro-pump design based on a pulsatile pumping system typically comprises a pumping chamber, into which a piston is pushed by a mechanical force, a valve on the inlet that controls flow such that it can only flow into the pumping chamber and a valve on the outlet that controls flow such that fluid can only exit the pumping chamber. When the piston is forced into the pumping chamber, and assuming the pumping chamber is full of fluid, the piston displaces a volume of fluid from the pumping chamber that is equivalent to the volume of the piston entering the pumping chamber. The displaced volume can only exit the micro-pump via the outlet because of the flow control exerted by the valves at the inlet and outlet.
When the piston retracts from the pumping chamber, a volume of liquid enters the pumping chamber that is equivalent to the volume of the piston that has retracted from the pumping chamber. Liquid can only enter the pumping chamber via the outlet because of the fluid control exerted by the valves on the outlet and the inlet.
Passive, normally closed one way membrane micro valve designs are commonly employed in micro pump design because they present a number of advantages. The construction of these micro valves typically comprises a membrane that serves to separate the fluid at the inlet to the pumping chamber from that present in the pumping chamber in the case of the inlet micro valve, or serves to separate the fluid present in the pumping chamber from that at the outlet of the pumping chamber in the case of the micro valve on the outlet. This membrane seals across a conduit that carries fluid across the micro valve structure. In normally closed micro valves, this membrane seals across the conduit and prevents the flow of fluid across the valve. The valve membrane seals onto a valve seat structure incorporated into the conduit and designed to accommodate at least part of the membrane and create a good fluidic seal. When the pressure on the side of the membrane from which liquid is allowed to enter and pass through the micro valve, exceeds the pressure on the opposite side of the membrane, the membrane releases its seal on the valve seat and fluid leaks from one side of the membrane to the opposite side. Liquid is prevented from flowing in the opposite direction since it is desirable that the valve membrane seals effectively against the valve seat, and this sealing is further improved by the increase in pressure on the side of the micro valve from which liquid is prevented from flowing.
The design features of micro pumps that contribute to inaccurate fluid delivery are known. For both liquid filling of the pumping chamber and fluid displacement out of the pumping chamber, it is advantageous if the pumping chamber is designed in such a way that the pumping piston displaces all the volume enclosed by the pumping chamber. This also includes any volume of liquid connecting the pumping chamber to the outlet of the micro valve and the volume of fluid connecting the pumping chamber to the outlet micro valve. In the case of a micro-pump designed for insulin delivery and which meets the current performance standard, it is not desirable that when the piston enters the pumping chamber the displacement of liquid varies by more than +/−2.5 ηl.
Also important, is that the pumping chamber volume fills completely with liquid and is devoid of air bubbles. The design of the pumping chamber therefore has to avoid features that could either trap air during initial filing of the pump with liquid or retains air bubbles if they accidentally enter the pumping chamber via the inlet. Air in the pumping chamber has the effect of reducing the volume of liquid displaced during the stroke volume. In the case of a micro-pump designed for insulin delivery and which meets the current performance standard, it is not desirable that the displacement of liquid when the piston enters the pumping chamber does not vary by more than +/−2.5 ηl. It is therefore desirable that the design of the micro valves at both the inlet and outlet of the pumping chamber integrates with the design of the pumping chamber, and that the resulting design avoids significant volumes that will not by expelled during the dispense stroke of the pump, and also avoids features that may encourage the retention of air bubbles within the pumping chamber volume.
The efficient delivery of the stroke volume can also be reduced if the pumping chamber is not completely contained within a rigid structure. In this respect, the presence of the valve membrane in both the inlet and outlet valves could result in at least part of the pumping chamber being flexible, absorbing some of the displaced volume created by the pumping piston and reducing the volume of fluid displaced. It is therefore important to ensure that while the valve membrane can flex to release the seal on the valve seat and allow liquid flow, it cannot flex at any other part of the valve. In the case of a micro-pump designed for insulin delivery and which meets the current performance standard, it is not desirable that the displacement of liquid when the piston enters the pumping chamber does not vary by more than +/−2.5 ηl. In relation to the design of micro valves, this requires that the micro valve volume that is connected to the pumping chamber does not expand by more than 2. or contract by more than 2.5 ηl.
Another important feature of the micro valve on the inlet of a micro pump is that the micro valve is required to allow flow of liquid as soon as the pressure at the micro valve inlet increases above the pressure at the outlet side of the inlet vale, and that this flow of liquid is unrestricted. This ensures that when the piston retracts from the pumping chamber, liquid enters the chamber from the inlet micro valve more efficiently, and the design of the micro pump can avoid having to employ methods and devices that increase the effective pressure of any reservoir providing liquid to the micro pump. Also it ensures that the pump can cycle quickly between fill strokes, when the piston retracts from the pumping chamber, and dispense strokes, when the piston enters the pumping chamber. To operate without the aid of a pressurised reservoir to supply the liquid to the micro pump, the micro valve on the inlet to the micro pump is required to allow flow at a pressure difference of less than 1 Atm. It is also required to allow at least 33 ηl/sec flow rate if the micro pump is to support the medication dispense rates that are typical of insulin delivery therapies using U100 insulin.
An important feature of the micro valve on the outlet of the micro pump is that this micro valve prevents flow from the inlet to the outlet of the micro valve except when the pumping piston enters the pumping membrane during the dispense stroke, and so prevents leakage of fluid through the pump when the pump is at rest. This could require that the micro valve at the outlet prevents flow at pressure levels that may exist inside the reservoir supplying the micro pump with liquid. These pressure levels may have been set to ensure efficient filling of the pumping chamber during the fill stroke. A micro pump delivering insulin at normal atmospheric conditions would require an outlet valve capable of preventing liquid flow upto a pressure difference across the valve membrane of 2 atms. If the reservoir supplying the insulin is pressurised to aid filling of the pumping chamber, the valve on the outlet of the pump may need to prevent flow at higher pressures.
Additionally, there is a need for medication delivery products that can be manufactured at low cost and in large numbers. These medication delivery systems are not intended to be used continuously but to be replaced on a periodic basis, and once the delivery system has operated for the intended duration. Medication delivery products designed for the delivery of insulin may require that a single device may be used for upto a period of three days before the components in contact with the insulin are discarded and replaced with new ones. This requires that the product can be manufactured and assembled using methods and processes that are cost effective. In addition, the device has to be manufactured from materials approved for use with the medication and can be sterilised prior to use using cost effective sterilisation processes. It is also required that the manufacturing and assembly processes produce devices that have equivalent performance characteristics. The combination of these requirements places imposes significant restrictions on the design of medication delivery devices.
A micro pump designed for use with certain medications may be required to operate efficiently even when particulate material is present in the medium. The insulin protein in commonly used diabetes medications is known to aggregate to form particles and fibres. These particles or fibres can be large enough to become trapped in certain features of a medication delivery system. Examples of these features are liquid sealing areas such as those found in membrane valves. This can cause the sealing of the valve to become less efficient and affect the performance of the medication delivery system.
A large variety of micro-valves have been described that could be used as part of the design for a micro pump. They include both passive and active devices. Passive micro valves are generally preferred over active valves due to their simple construction and design. Passive micro-valves are predominantly designed to provide fluid flow selectively in one direction, requiring a build-up of pressure by the fluid on one side of the valve, and in the direction the micro-valve is designed to allow flow.
In general the requirements for a one-way, passive microvalve are that the valve allows flow of the fluid in the intended direction of flow, while preventing the flow of fluid in the reverse direction. For this purpose, sealing between the parts incorporated into the design to prevent reverse flow of fluid is of primary importance. Conversely, these parts are required to break the seal formed between them to allow fluid to flow in the intended direction. In some cases, it is desirable if the breaking of this seal only occurs above a certain build up of fluid pressure in the direction of intended flow.
A variety of passive micro-valve designs have been proposed. A large number rely on silicon micro-fabrication techniques and are constructed from silicon or one of its derivative materials (silicon nitride, silicon oxide etc.). The use of silicon materials in the construction of micro-valves presents a singular problem. The stiffness of the materials and the hardness of the materials, combine to making sealing of micro-valves constructed in this way a challenge. These two physical characteristics of the candidate materials prevent the sealing surfaces to conform to the surface irregularities of the other and provide efficient fluidic sealing. In fact, it is almost certainly the case that if the sealing surfaces could not be produced to such high flatness and accuracy using microfabrication technologies, these micro-valves would not be able to seal sufficiently to create an efficient micro-valve. However, even when these valves operate sufficiently well, the use of these micro-valves to valve fluids with particulate material suspended in them, or in applications that support the build up of surface fouling layers, tends to accentuate the problem of creating effective seals between hard and stiff materials.
The use of elastomeric materials in the construction of fluid controlling valves has been known for some time. Specifically, the use of elastomeric materials in the construction of micro-valves has also been described. The use of elastomeric materials for these purposes provides an advantage since they can continue to provide the effective sealing for which they are responsible even in the presence of particles in the liquid.
A review of the current state of the art finds that a variety of micro valve designs have been proposed that incorporate an elastomeric membrane. Each design incorporates a valve membrane and a valve seat. The designs are different in the arrangement of the membrane relative to the valve seat design.
The prior art describes valves where the valve membrane seals onto a valve seat that is essentially planar to the valve membrane and essentially parallel to that membrane. These designs have been embodied as essentially planar membranes sealing onto planar valve seats, essentially planar membranes sealing onto a raised valve seat and a further modification of this embodiment to include raise ridges on the valve seat to enhance the sealing between the membrane and the valve seat. In some embodiments the valve seat is reduced to form only a raised annular ring onto which the membrane seals. In other embodiments, valves have been described where the membrane is further modified to include raised annular ridges that enhance the sealing of the membrane onto the valve seat.
U.S. Pat. No. 3,827,456A describes a valve design that incorporates many of the features described above. U.S. Pat. No. 3,827,456A describes a valve where the elastomeric valve membrane has a central hole at the centre of a annular raised bead that seats on top of an annular valve seat so that it seals on the surface at the top of the valve seat. The elastomeric membrane is stretched over the seat to provide an efficient sealing force. The inlets to the vale are arranged circumferentially around the annular valve seat. The valve membrane also has a thickening of the external annular portion to facilitate its positioning into the valve structure.
Valve designs are further characterised by having one of at least two embodiments. The first incorporates a valve membrane that is held in close proximity to the valve seat and relies on at least some influence from the fluid in the valve to affect its sealing onto the valve seat. These valves seal only when the pressure difference between one side to the sealing membrane and the other is high enough and in the correct direction to seal the membrane against the valve seat. The second incorporates a valve membrane that is held against the valve seat either by the tension in the valve membrane or by a structure used to force the membrane against the valve seat. An example of the first is a membrane stretched over a pillar shaped valve seat. An embodiment of the latter is a membrane held in place by a spring, acting on the membrane to force it against the valve seat.
U.S. Pat. No. 4,493,339A describes a valve having a valve membrane with a raised annular section that when seated onto a flat valve seat creates the sealing force for the valve. The valve membrane also has a thickened outer annular segment that is used to locate the membrane into the valve construction and help retain the valve under correct tension against the valve seat. To aid this, prior to assembly into the valve a cross sectional view of the valve membrane shows that the raised annular section that forms the seal for the valve is lower than the edge of the thickened outer annular segment.
U.S. Pat. No. 3,176,712A describes a valve incorporating a valve membrane stretched over a semi-spherical valve seat. The valve seat is located over a base pate perforated to allow fluid to past through it. Fluid can then leak past the seal between the valve seat and the valve membrane if there is sufficient pressure to do so. The membrane has a centrally located hole that is normally blocked by the semi spherical valve seat, but through which fluid flows when the seal is broken.
GB 2443260 describes a micro valve comprising a valve membrane stretched over a valve seat located onto the projecting surface of a pillar. Liquid enters the valve through a hole centrally located in the valve seat pillar and, when the pressure on the inlet to the valve is high enough, passes past the seal created between the membrane and the valve seat. The membrane has at least one hole to allow fluid to pass through the membrane once it has broken past the seal between the membrane and the valve seat.
A number of valve designs describe valve membranes that are structured to provide the membrane with regions of different structural strength, and to allow the valve to operate.
U.S. Pat. No. 4,143,853A describes a valve based on a valve membrane that has a slit cut into the central portion such that the slit opens to allow flow but seals when flow is reversed through the valve. The valve membrane has a thickening around the central flexible portion to provide the membrane with a ring of structural material that assists in keeping the membrane in tension and the slit in a normally closed position. U.S. Pat. No. 4,770,740A describes a micro valve and a method for manufacturing it that comprises a flexible nickel valve membrane that has an inner portion that seals against the valve seat and creates the sealing for the valve. The valve membrane is fabricated from a single sheet of nickel that is structured to provide the flexible valve sealing portion and a rigid frame that retains this flexible portion in position and under tension. The two are connected by a series of supporting arms.
Valve designs that incorporate a flexible membrane forcibly held against a valve seat are preferred in the design of micro pumps where very low displacement volumes are common. They are also preferred for other very low flow rate applications. These valve designs have the greatest potential to prevent reverse flow of liquid even at very low back pressures. The micro-valve design creates a structure where only a very small section of the device is important to the sealing performance of the micro-valve. Moving the sealing surface away from the inlet hole creates new opportunities for micro-valve designs.
Micro-valve designs such as described in GB2443260B require that the pillar that comprises the valve seat is large enough to allow a through hole to be formed in the centre of the pillar to provide the inlet to the micro-valve. Current fabrication technologies restrict the minimum radius that can be achieved for this through hole, and also restrict the wall thickness between the hole and the outer diameter of the pillar. Furthermore, the total cross-section area of the inlet hole available for fluid flow is restricted by these limitations.
CA1301244C describes a valve device that also seals at a junction between the sealing membrane and the surface of the valve seat. In one embodiment CA1301244C describes the use of a conical valve seat as a further improvement to the device. However, CA1301244C describes a relatively large valve that cannot be readily replicated using micro fabrication techniques and for the construction of a micro-valve. Also, the limitations described in relation to GB2443260B apply to this design. Specifically, the location of the inlet for the valve at the centre of the valve seat and the limitations imposed by fabrication techniques relative to this feature.